Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study

Chen, C.-L.; Chen, N.-C.; Wu, Fu-Zong; Wu, Ming‐Ho

doi:10.1007/s00198-020-05391-3

Cited by 37 publications

(41 citation statements)

References 33 publications

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“…104 It is reassuring that studies in patients with (advanced) CKD did not detect any vascular safety signals. 79,[106][107][108] Some caution is warranted since these studies were characterized by either small sample size or short follow-up. It is unlikely that the absence of detrimental effects on calcification in bisphosphonatetreated individuals are explained by the fact that bisphosphonates are analogues of pyrophosphate, which is a potent vascular calcification inhibitor, as conventional doses of bisphosphonates fail to yield circulating concentrations that are sufficient to exert direct anti-calcifying effects.…”

Section: Low Bone Turnover and Outcomes In Ckdmentioning

confidence: 99%

“…On the other hand, treatment with calcimimetics, 112 long-term follow-up after parathyroidectomy, 113 adequate treatment with active vitamin D, 114 or antiresorptive agents 115 may induce a more balanced reduction of bone turnover, while clinical evidence to date indicates an absence of negative cardiovascular effects in non-CKD patients 116,117 and in patients with advanced CKD. 79,100,108…”

Section: Low Bone Turnover and Outcomes In Ckdmentioning

confidence: 99%

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Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Haarhaus

Evenepoel

2021

Kidney International

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Section: Low Bone Turnover and Outcomes In Ckdmentioning

confidence: 99%

Section: Low Bone Turnover and Outcomes In Ckdmentioning

confidence: 99%

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Haarhaus

Evenepoel

2021

Kidney International

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“…Recently, the concept that low bone turnover, per se, increases the risk for negative outcomes in CKD has been challenged [3]. While some systemic pathophysiologic processes associated with low bone turnover, e.g., malnutrition, chronic inflammation, or diabetes mellitus, are also frequently associated with increased mortality and CV complications [33,34], other forms of reduced bone turnover, e.g., as seen in treatment with antiresorptive agents, are not [35,36]. In some previous studies, correction for indicators of malnutrition and inflammation attenuated the observed association of low PTH states with mortality [3].…”

Section: Discussionmentioning

confidence: 99%

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

et al. 2021

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Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

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“…All these results may seem a medical paradox, as it was demonstrated that OPG is an anti-calci cation factor 24 and low OPG maybe associated with poor prognosis in some HD patients 25 . Studies have also demonstrated that denosumab, an endogenous RANKL inhibitor which mimics the natural action of OPG, may suppress the progression of arterial calci cations 26,27 . Further studies are warranted before a sound hypothesis for this seeming contradiction can be set.…”

Section: Discussionmentioning

confidence: 99%

Arterial Calcifications and Osteoprotegerin in Chronic Hemodialysis Patients – Impact on 6 Years Survival

Moldovan

Rusu

Potra

et al. 2021

Preprint

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The study goal was to assess the impact of each type of arterial intimal calcifications (AIC) and arterial medial calcifications (AMC) identified on ultrasound, of osteoprotegerin (OPG), mineral metabolism markers and other features on all-cause and cardiovascular mortality in chronic hemodialysis patients. Ultrasound was performed in 87 patients on the carotid and femoral arteries, and the severity of AIC and AMC was assessed calculating a score according to the extension of calcification. The cut-off value for OPG determined using ROC was 4.9 pmol/L for all-cause and cardiovascular mortality. Patients with higher serum OPG levels presented higher mortality rates. Our results revealed that AIC, high OPG, low ankle-arm index, presence of diabetes, smoking status, and lack of arteriovenous fistula are associated with all-cause and cardiovascular mortality in univariate regression analysis. Multivariate analysis identified AIC scoring based on the segmentation method as an independent predictor of all-cause and cardiovascular mortality, along with increased OPG levels. AMC scoring was not a predictor of mortality. Identifying and scoring AIC on ultrasound and measuring OPG levels, as a basis of the HD patient assessment may become valuable tools in clinical work, as these have an impact on death toll.

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Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study

Cited by 37 publications

References 33 publications

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease

Arterial Calcifications and Osteoprotegerin in Chronic Hemodialysis Patients – Impact on 6 Years Survival

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